This document summarizes oncogenesis, the process by which normal cells are transformed into cancer cells. It discusses how proto-oncogenes can become activated oncogenes through mutations, increased expression, or chromosomal rearrangements. Oncogenes code for proteins involved in cell growth and division. The document also describes various causes of oncogenesis like genetic/epigenetic changes, DNA damage from endogenous or exogenous sources, field defects, and oncogenic viruses that activate proto-oncogenes or inactivate tumor suppressor genes. The mechanisms of viral oncogenesis and classification of viral oncogenes into growth factors, receptors, signal transducers and transcription factors are summarized as well.

2. Presented to :
Mam Sanya
Presented by :
Ahmad Raza
Roll NO:
151835/37210
PRESENTATION OF DEVELOPMENTAL BIOLOGY

3. Presentation topic:
Oncogenesis

4. Oncogenesis:
The induction or formation of tumors”
OR
“Oncogenesis also called Carcinogenesis, or
tumorigenesis, is the formation of a cancer,
whereby normal cells are transformed into cancer
cells. The process is characterized by changes at the
cellular, genetic, and epigenetic levels and
abnormal cell division

5. Oncogene
An oncogene is a gene that has the potential to
cause cancer. In tumor cells, they are often
mutated and/or expressed at high levels. Most
normal cells will undergo a programmed form of
rapid cell death (apoptosis) when critical functions
are altered and malfunctioning.

6. Proto oncogene
A proto-oncogene is a normal gene that
could become an oncogene due to
mutations or increased expression. Proto-
oncogenes code for proteins that help to
regulate cell growth and differentiation.
Upon acquiring an activating mutation, a
proto-oncogene becomes a tumor-inducing
agent, an oncogene.

7. Illustration of how a normal cell is converted
to a cancer cell, when an oncogene becomes
activated

8. Causes of oncogenesis:
• Genetic and epigenetic
• DNA damage
• Contribution of field defects
• Genome instability

9. Genetic and Epigenetic
Many of these changes are mutations, or changes
in the nucleotide sequence of genomic DNA. There
are also many epigenetic changes that alter
whether genes are expressed or not expressed.
Aneuploidy, the presence of an abnormal number
of chromosomes, is one genomic change that is not
a mutation, and may involve either gain or loss of
one or more chromosomes through errors in
mitosis.

10. Cancer is caused by a
series of mutations. Viral
infections contribute to the
process through genetic
alteration.
Mutations Leading to
Increased Cell Division

11. DNA damage
DNA damage is considered to be
the primary cause of cancer. More
than 60,000 new naturally occurring
DNA damages arise, on average, per
human cell, per day, due to
endogenous cellular processes.

13. Cause of DNA damage:
There are main two agents that cause
DNA damage these are :
•Exogenic agent
• Endogenic agents

14. Exogenous agent:
Additional DNA damages can arise from exposure
to exogenous agents. As one example of an
exogenous carcinogenic agent, tobacco smoke
causes increased DNA damage, and these DNA
damages likely cause the increase of lung cancer
due to smoking. In other examples, UV light from
solar radiation causes DNA damage.

15. Endogenous agent
DNA damages can also be caused by endogenous
(naturally occurring) agents. Macrophages and
neutrophils in an inflamed colonic epithelium are
the source of reactive oxygen species causing the
DNA damages that initiate colonic tumorigenesis,
and bile acids, at high levels in the colons of
humans eating a high fat diet, also cause DNA
damage and contribute to colon cancer.

16. Deficiency in DNA repair
A deficiency in DNA repair would cause more
DNA damages to accumulate, and increase
the risk for cancer. For example, individuals
with an inherited impairment in any of 34
DNA repair are at increased risk of cancer
with some defects causing up to 100%
lifetime chance of cancer.

18. Contribution of field defects
The term "field concretization" was first used in
1953 to describe an area or "field" of epithelium
that has been preconditioned by largely unknown
processes so as to predispose it towards
development of cancer. Since then, the terms "field
concretization" and "field defect" have been used
to describe pre-malignant tissue in which new
cancers are likely to arise. Field defects have been
identified in association with cancers and are
important in progression to cancer

19. Genome instability
Genome instability (also genetic instability or
genomic instability) refers to a high
frequency of mutations within the genome of
a cellular lineage. These mutations can
include changes in nucleic acid sequences,
chromosomal rearrangements or aneuploidy.

20. Oncogenic viruses
Oncogenic viruses can be divided into 2
groups, based on their genetic material
as:
• DNA tumor viruses and
• RNA tumor viruses.

21. Generalization about Viral
Transformation
RNA viruses activate oncogenes
DNA viruses negate tumor suppressors

22. DNA tumor viruses
Virus can containing either single stranded
or double stranded DNA.
Examples of DNA viruses are:
Adenoviridae, Herpesviridae,
Papillomaviridae, Polyomaviridae, Poxviridae
etc.

23. Cell cycle of DNA tumor
viruses
DNA tumor viruses DNA tumor viruses have 2 life forms.
•In permissive cells, viral replication causes cell lysis and
cell death.
•In no permissive cells, viral DNA is mostly integrated into
the different sites of cell chromosomes. It encodes binding
proteins and inactivates cell growth, regulating proteins like
p53 and retinoblastoma. The cell is transformed as a result
of the expression of proteins that control viral and cellular
DNA synthesis

27. RNA tumor Viruses
RNA virus contains predominantly single
stranded RNA; although viruses do exist that
contain double stranded.
Examples of RNA viruses:
Alpharetrovirus, Delta retrovirus,
Gammaretrovirus, Retroviridae, Flaviviridae

28. Retroviridae a RNA tumor viruses
Retroviruses (family Retroviridae) are enveloped, single
strande RNA viruses that replicate through a DNA
intermediate using reverse transcriptase.
This large and diverse family includes members that are
oncogenic, are associated with a variety of immune system
disorders, and cause degenerative and neurological
syndromes.

30. Cell cycle of RNA tumor
viruses
All oncogenic RNA viruses are retroviruses. Retroviruses or
RNA Tumor viruses replicate by a unique manner by an
enzyme, reverse transcriptase (RT) carried by the viruses.
RT constructs a DNA copy of the RNA genome of the virus
and the DNA copy (pro-phage) becomes integrated with
DNA of the host cell, where it may remain latent for
variable periods. Only when activated, the integrated
provirus acts as template for translation of progeny viral
RNA and cell transformation.

31. Retroviruses
31
Scanning EM
Transmission EM
Envmatrix
capsid RNA

32. 1. Attachment of the virion to a specific cell surface receptor
2. Penetration of the virion core into the cell
3. Reverse transcription within the core structure to copy the genome RNA into
DNA
4. Transit of the DNA to the nucleus
5. Integration of the viral DNA into random sites in cellular DNA to form the
provirus
6. Synthesis of viral RNA by cellular RNA polymerase II using the integrated
provirus as a template
7. Processing of the transcripts to genome and mRNAs
8. Synthesis of virion proteins
9. Assembly and budding of virions
10. Proteolytic processing of capsid proteins
Retrovirus replication cycle

35. Retroviral Life Cycle
35
Late events:
From time when integrated
provirus is expressed until
virus has been released
Early events:
from viral binding and
entry until the time the DNA
copy of the viral genome is
integrated into the host
cell’s chromosome

36. Latent vs. active infection
36
In latent infection- retroviral genome is present but is not
transcribing viral genome or mRNA for structural proteins.

37. Mechanism for viral-oncogenesis
• Oncogenes affect the signal transduction process in
an aberrant manner. (RNA tumor viruses) Growth
factor expression
• Growth factor receptor
• Cytoplasmic or membrane-bound kinases
• Transcription factors
2. Inactivation of Tumor-suppressor genes (DNA tumor
viruses)
• Uncontrolled proliferation
• Inhibition of Apoptosis

38. Classification of viral oncogenes
Oncogenes can be categorized into 5 groups in
terms of the biochemical and functional
properties of protein products of
protooncogenes.These groups are
 Growth factors,
 Growth factor receptors,
 Signal transducers,
 Transcription factors.

39. Growth factor:
Growth factors are secreted polypeptides that
stimulate the proliferation of target cells and have
extracellular signal functions. Target cells must have
a specific receptor to be able to respond to a
specific type of growth factor. As an example of
growth factors, platelet-derived growth factor
(PDGF), which is composed of 2 polypeptide chains,
induces the proliferation of fibroblasts

40. Growth factor receptors
Some viral oncogenes are modified versions of normal
growth factors that have intrinsic tyrosine kinase activity.
Growth factor receptors have a characteristic protein
structure that has 3 main parts:
• the extracellular ligand-binding area,
• the transmembrane and
• the intracellular tyrosine kinase catalytic areas. Growth
factor receptors play a role in the regulation of normal
cell growth.

41. Signal transducers:
The process by which a cell responds to substances in
its environment. The binding of a substance to a
molecule on the surface of a cell causes signals to be
passed from one molecule to another inside the cell.
These signals can affect many functions of the cell,
including cell division and cell death. Cells that have
permanent changes in signal transduction molecules
may develop into cancer.

42. Transcription factors(TFs)
•TFs are essential for controlling gene expression during
normal physiological conditions and disease.
•High proportion of oncogenes and tumor suppressors encode
TFs.
•Hallmarks of cancer, such as control of cell cycle, protection
from apoptosis, induction of angiogenesis, proliferation,
migration and invasion are controlled by gene expression
patterns and signaling pathways that are regulated by TFs.
•Up regulation of TFs is related to increased resistance to
drugs used in cancer treatment.
•TFs may represent an important target for the treatment of
several types of cancers.

43. Mechanisms of oncogene
activation
The activation of oncogenes requires genetic
changes in cellular proto-oncogenes. Oncogenes
are activated by 3 genetic mechanisms:
a) Mutation
b) Gene amplification
c) Chromosome rearrangements

45. Mutations:
Mutations activate proto-oncogenes through
structural alterations in their encoded proteins. These
alterations, which usually involve critical protein
regulatory regions, often lead to the uncontrolled,
continuous activity of the mutated protein. Various
types of mutations, such as base substitutions,
deletions, and insertions, are capable of activating
proto-oncogenes

48. Gene Amplification
Gene amplification is a copy number increase
of a restricted region of a chromosome arm. It
is prevalent in some tumors and is associated
with overexpression of the amplified gene(s).
Amplified DNA can be organized as extra
chromosomal elements, as repeated units at a
single locus or scattered throughout the
genome.

49. Chromosomal rearrangement
Chromosomal rearrangements can lead to hematologic
malignancy via two different mechanisms:
(1) the transcriptional activation of proto-oncogenes or
(2) the creation of fusion genes.
Transcriptional activation, sometimes referred to as
gene activation, results from chromosomal
rearrangements that move a proto-oncogene close to
an immunoglobulin or T-cell receptor gene

50. Gene activation:
The process of activation of a
gene so that it is expressed at a
particular time. This process is
crucial in growth and
development.

51. Fusion of genes:
Fusion genes can be created by chromosomal
rearrangements when the chromosomal
breakpoints fall within the loci of two different
genes. The resultant juxtaposition of segments from
two different genes gives rise to a composite
structure consisting of the head of one gene and
the tail of another. Fusion genes encode chimeric
proteins with transforming activity.

52. Translocation
Transcription